Team Metabolic Health

A study in overweight individuals concludes that misaligned body clocks are associated with raised metabolic risk factors. The findings show these metabolic changes vary between males and females. Realigning the body clock with sufficient sleep could help reduce the negative health implications of overweight and obesity, researchers say.

Circadian rhythms are 24-hour cycles that the body goes through each day — an internal “body clock.” These cycles include fluctuations in levels of hormones and neurotransmitters and drive the daily sleep-wake cycle. A recent study from researchers at Oregon Health & Science University (OHSU) shows that people with overweight or obesity whose circadian rhythms are poorly aligned may experience negative metabolic effects.

A study in people with overweight and obesity found that misaligned circadian rhythms are linked to raised metabolic risk factors. skaman306/Getty Images

The findings, published August 20 in The Journal of Clinical Endocrinology & Metabolism, suggest these negative effects vary significantly between males and females.

Readjusting the body clock could potentially reduce some of the risks associated with overweight and obesity, researchers say, although more evidence is needed to determine these effects.

How does overweight or obesity affect sleep?

Scientists have known for many years that getting enough good quality sleep is essential for good health. However, many people in our modern society are getting fewer hours of shuteye than ever. Research has also shown a close relationship between inadequate sleep and weight gain. For instance, the authors of a review on the subject concluded that short sleep duration was significantly associated with the risk of developing obesity in the future, but that long sleep duration was not. Research also suggestsTrusted Source that circadian misalignment may be linked to increased energy intake and obesity riskTrusted Source. Jacob Teitelbaum, MD, a board-certified internist and expert in chronic fatigue syndrome, fibromyalgia, sleep, and pain, explained why circadian rhythms are so important.

“The circadian rhythm is the critical ‘orchestra conductor’ for your body,” he told Healthline. “It regulates the proper timing of your hormonal and immune systems, and numerous other functions.” Teitelbaum was not involved in this study.

Studies have shown that circadian misalignment — which could mean feeling awake while the internal body clock is promoting sleep or eating when the body should be sleeping — is associated with less energy expenditure during the day.

In other words, people in this misaligned state burn fewer calories. Not sleeping enough is also linked to consuming more calories throughout the following day.

The relationship is complex, though, and researchers are still trying to understand precisely how body clock misalignment and insufficient sleep impact metabolic health.

What’s the relationship between circadian rhythm and obesity?

In the latest study, the scientists recruited 15 females and 15 males, all with overweight. They measured their body composition and took blood samples.

They also assessed their dim-light melatonin onset (DLMO). Melatonin is an important hormone that helps maintain circadian rhythms. As the day draws to a close and light levels fall, the brain produces melatonin. As levels increase, the individual becomes increasingly sleepy.

DLMO measures when melatonin release begins in dimly-lit conditions. Because melatonin release is a sign that the body clock is preparing an individual for sleep, scientists use DLMO as a marker of circadian rhythm phase.

By measuring the time difference between melatonin beginning to rise and the participant going to sleep, the researchers gauged the level of circadian rhythm misalignment.

Study co-author Brooke Shafer, PhD, a postdoctoral researcher with the Sleep, Health, & Chronobiology Laboratory at OHSU Portland Campus School of Nursing explained why this is important:

“Your body has a time that it starts to signal the brain to fall asleep, and if we try to sleep really close to that time, we may have trouble sleeping or have a lower quality sleep,” Shafer told Healthline.

Following the week-long study, the researchers identified sex-specific effects of body clock misalignment.

1. Misaligned males had:
2. Higher levels of abdominal fat
3. Higher levels of blood fat (triglycerides)
4. A greater risk of metabolic syndrome
5. Misaligned females had:
6. A higher percentage of overall body fat.
7. Higher blood sugar levels.
8. A higher resting heart rate.

Shafer shared that she was surprised by the sex differences. “These findings really emphasize that there is no one-size-fits-all approach to maintaining healthy behaviors,” she said.

In particular, she explained, “the sex-specific differences in how sleep habits affected glucose and triglyceride levels were quite notable.”

This is important because individuals who have high levels of blood fat or blood sugar have an increased risk of heart disease.

These findings suggest that “circadian disruption may not only promote a trajectory of weight gain but could also contribute to negative health consequences in a sex-dependent manner in those already with overweight/obesity,” the study authors wrote.

The researchers hope that optimizing circadian alignment could help reduce the risk of poorer health outcomes, particularly in people with overweight or obesity.

Shafer said the team will continue to study the impact of circadian rhythm misalignment.

“Our next steps are to look at sex-specific differences in health markers for individuals who are vulnerable to extreme sleep disturbances, such as those who work during nighttime hours,” she said.

How to realign circadian rhythm

The current study is small-scale, so scientists need to carry out more work to confirm the results. However, a number of studies have shown that a misaligned body clock is linked to negative health outcomes.

The good news is that most people can readjust their body clock with good sleep habits.

This could mean that an individual with overweight might be able to reduce their risk of metabolic diseases by working to realign their circadian rhythms. However, trying to maintain a healthy weight should still be the primary goal.

Chelsea Perry, PhD, owner of Sleep Solutions in Westborough, MA, not involved in the study, and member of the American Academy of Sleep Medicine, suggested the following tips to for getting your internal body clock back on track:

1. Maintain a consistent sleep schedule, even on weekends.
2. Get exposure to natural light, especially in the morning.
3. Limit screen time and bright lights in the evening. This helps signal to your body that it is time to wind down.
4. Gradually adjust your bedtime and wake time by 15–30 minutes each day to help ease your body back into its natural rhythm.

Cherilyn Davis, MD, a board-certified pediatrician with Elliston Pediatrics, likewise not involved in the study, offered additional tips to optimize sleep:

Avoid things that may disrupt sleep, like drinking caffeinated drinks before bedtime.

Make your sleeping space comfortable, cool, and dark.

Avoid napping or exercising late in the day, as this may make you less tired at night and disrupt circadian rhythm.

Takeaway

A new study concludes that people with overweight and have a misaligned body clock may be at a greater risk of metabolic disease. Conversely, the authors hope that realigning circadian rhythms might help reduce these risks.

Credit: healthline.com

Team Metabolic Health

We know that food is fuel for our bodies, but what foods make the best fuel for our brains?

“The foods that we eat, we think, ‘OK, we break those foods down and that turns into energy.’ Well, it’s a little bit more complicated than that,” said Tegan Mansouri, clinical assistant professor at the University at Buffalo School of Public Health. 

According to a recent study published in the JAMA Network Open journal, the correct answer is foods that are anti-inflammatory.

What You Need To Know

A study published in the JAMA Network Open journal found that eating a diet of anti-inflammatory foods can help lower the risk of dementia by 31%.

The study looked at the diets of people with cardio metabolic diseases such as type 2 diabetes or high blood pressure.

The study also found that for those with cardio metabolic diseases who had an anti-inflammatory diet, it also contributed to two more years of life before onset of dementia.

“Anti-inflammatory foods [like] fruits, vegetables and also foods high in fiber like whole grains, those types of foods contribute to reducing the inflammation in our body,” Mansouri said. “And we know that inflammation is associated with decreased grey matter, decreased white matter and overall increased cognitive decline.”

The study looked at the diets of people with cardio metabolic diseases such as type 2 diabetes or high blood pressure.

“What they found was that even those who had already been diagnosed with cardiometabolic disease, they were able to get the benefits of that anti-inflammatory diet that reduced their risk of dementia by 31%,” said Mansouri.

Meaning whole foods like fruits, veggies and whole grains help reduce the overall inflammation throughout our body. 

“The more we incorporate that in our diet, the less we’re consuming foods that don’t have as much nutrient density,” said Mansouri.

But it doesn’t mean that eating healthy has to be all work and no play.

“It’s so much less that eating a bowl of ice cream is going to cause inflammation and it’s so much more about the overall balance of the diet,” Mansouri said.

Credit: Spectrum News

Team Metabolic Health

Pix Credit: Wion News

Across the world, there are over five billion people whose diets do not include iodine, vitamin E, and calcium. Indians across all age groups are believed to be deficient in iron, calcium, and folate, which are essential for health, because of inadequate consumption of micronutrients, according to a recent study. According to a study published in The Lancet Global Health journal, people in India are not consuming a proper nutritional diet which is said to be resulting in micronutrient deficiencies. Micronutrients, which include vitamins and minerals, play a significant role in maintaining proper bodily functions. They are essential in smaller amounts like fats and carbohydrates are vital components for good health.

Credit: Wion News

Team Metabolic Health

5 ChatGPT prompts to identify bad clients before you work with them 

What if you could spot problematic clients before they derail your projects and cost your peace of mind? What if you could transform your client selection process to guarantee mutually beneficial partnerships? What if you only worked with awesome clients, who understood your value and were grateful for your work? It’s all possible.

Not everyone is your client. And letting everyone in is a false economy. Change how you filter to transform your business and disposition.

Chris Do is founder and CEO of The Futur, a business school for creatives, providing coursework, community and online coaching to help creative entrepreneurs succeed. Do is an Emmy award-winning designer, content creator and podcast host, and has run a design business for 22 years. He’s on a mission to teach 1 billion people to make a living doing what they love, and with books, courses, and a YouTube channel with over 2 million subscribers, he’s doing just that. Do believes that asking the right questions can help creative professionals avoid nightmare client situations and set the stage for successful collaborations.

Combining Do’s teaching on client relationships with powerful prompts led to 5 ChatGPT prompts to identify potential client issues before they arise. The prompts were designed and tested by Prompt Entrepreneur Kyle Balmer, an international trainer in AI for business and entrepreneurship with 50,000 newsletter readers and 25,000 students of his prompt engineer courses.

Use these ChatGPT prompts to improve your client screening process and set the foundation for successful projects. Copy, paste and edit the square brackets in ChatGPT, and keep the same chat window open so the context carries through.

Protect your business: detect difficult clients early with 5 ChatGPT prompts

Uncover the gap between desire and results

Unhappy clients make bad clients. And unhappiness comes from the difference between expectation and results. “I’m always looking for a gap. I’m looking for a problem to solve,” explains Do.

The problem might not be them, it might be you. Understand the disconnect between what clients want and what they’re currently getting to reveal potential challenges and opportunities. If a relationship started off great and then it turned bad, figure out what went wrong and make sure what you’re delivering is up to scratch. Your service can always improve. Here’s Balmer’s prompt.

“You are a business analyst specializing in identifying gaps between client goals and current results. Based on this initial client statement [insert potential client’s description of their needs], identify potential gaps between their desired outcomes and current situation, [add details of their desires and realities], and suggest three probing questions to better understand these gaps, as well as possible red flags (theirs or ours) that might indicate unrealistic expectations or misalignment.”

Explore the client’s future vision

Travel forward in time with your client to understand what success looks like from their point of view. Are they unrealistic from the start, or can you ultimately satisfy their needs? Chris Do recommends you ask your potential client this question to gauge their clarity and commitment: “If we were having this discussion 3 years from today and you were looking back over those 3 years, what has to have happened in your life both personally and professionally for you to feel happy with your progress working with us?”

Ask every client this question to see if you’re up to the challenge of working with them. Get help assessing their response with this prompt.

“You are an expert in analyzing responses to the question I ask potential clients before working with them: “If we were having this discussion 3 years from today and you were looking back over those 3 years, what has to have happened in your life both personally and professionally for you to feel happy with your progress working with us?” Based on this client response [insert client’s answer to the 3-year question], evaluate the clarity of their vision, and potential misalignments between their goals and my services, [describe your services].”

Assess the client’s willingness to change

“Everyone wants to be a bodybuilder, but nobody wants to lift no heavy-ass weights,” said Ronnie Coleman. “Everybody wants different results, but they don’t want to do anything different,” said Chris Do.

If you’re willing to put in the work to make a client relationship a success, you want the same in return. You can’t help someone who doesn’t want to be helped. This prompt created by Balmer, helps identify clients who are truly ready for transformation.

“You are a change management consultant. Given this summary of a potential client’s current practices and desired outcomes: [insert summary], analyze the scale of change required to achieve their goals, with potential resistance points or areas of discomfort. Next, suggest three questions I could ask them, to gauge their genuine willingness to implement necessary changes.”

Evaluate the client’s perspective on expertise

Is the client going to welcome your opinion and let you do your thing, or question every decision and micromanage the process? Spot the warning signs early. While Do knows that “clients will know their own business best,” they have to be open to professional expertise.

Identify clients who might be overly prescriptive or dismissive of your work. Paste your emails or record your sales calls and upload the transcripts along with this prompt. Read between the lines with ChatGPT.

“You are an expert in client-consultant relationships. Based on these statements from a potential client about their project needs [insert client statements, potentially from a triage call], assess their openness to professional advice and new perspectives. Then, identify potential signs of micromanagement or distrust in expert opinions. Finally, suggest three tactful ways to address any concerning attitudes about the value of your expertise.”

Identify potential scope creep

When you quote for a body of work that ends up being double, that’s scope creep. It’s common for creatives. Everyone gets excited about what could be done. One conversation leads to another and before long you’ve committed to a long list of tasks within your current brief.

But improving at quoting and requoting can help you handle this problem. “I’m not afraid of the scope list that comes out,” says Do. He has a winning system. Understand and apply comprehensive project planning to make sure you’re covered. This prompt helps anticipate and address potential scope issues.

“You are a project management specialist focusing on scope definition. Given this initial project description from a potential client [insert project description], identify: three areas where scope creep is likely to occur, questions to ask the client to clarify project boundaries, and potential red flags in the client’s language that might indicate unrealistic expectations about deliverables or timelines.”

Identify problematic clients before you commit

Use these prompts to apply the wisdom of Chris Do, improving your client screening process and setting the stage for more successful, mutually beneficial projects. Dig into the gap between expectation and reality to never come up short, and know what your client wants in the long term. Assess their willingness to change, know their openness to professional expertise, and pre-empt scope creep so it doesn’t catch you out.

Uncover crucial information and make informed decisions about any client partnership you take any further.

Credit: Forbes

Team Metabolic Health

India will overtake the US as home to the largest software developer community in the world by 2027, converging with the rise of artificial intelligence (AI), GitHub chief executive Thomas Dohmke said. Dohmke told the ET World Leaders Forum that tens of millions of developers in India are creating the digital public infrastructure of the future, fueling economic growth. GitHub is a developer platform that allows developers to create, store, manage and share their code. The company was acquired by Microsoft in 2018.

GitHub Chief Executive Thomas Dohmke

Faster adoption of AI is leading tens of millions of techies to create digital public infrastructure of the future and fuel economic growth. “Developers drive GDP growth and technological progress to the tune of trillions of US dollars. And the opportunity goes further because software developers are adopting AI faster than any other sector of the global workforce,” Dohmke said. The executive has been at the forefront of GitHub’s integration of OpenAI’s GPT models, creating the world’s first AI developer tool that helps autocomplete software coding, GitHub Copilot.

“Developers are already 55% faster using Copilot, an acceleration not seen since the industrial age,” Dohmke said. For India, AI is the opening chapter of a new book of opportunity, he said. “We are living in an era where every company can and must become an AI company… each company who embraces this and become early adapters will exist on a whole other spectrum of productivity entirely.”

Dohmke said companies must first identify gaps in productivity, and then fill them using AI. “Identify the productivity gaps in your company at large, because AI in search of a problem is pointless. AI for the sake of AI’s pointless, AI is a solution to the problem, that is the whole point.”

Citing GitHub’s example, Dohmke said experimenting with AI has brought down customer support volumes by over 20% year-on-year, urging companies to infuse a culture of AI integration.
“Every person in your organisation needs to buy into this culture from the leadership team down to the entry level employees and that starts with leading by example. We need leaders who will model what it looks like to leverage automation in their everyday lives,” Dohmke said.
Credit: Economic Times

Team Metabolic Health

Tirzepatide, the active ingredient in the popular weight loss drug Zepbound, has been shown to reduce the risk of developing type 2 diabetes in obese or overweight adults with pre-diabetes by a huge 94 percent. The results reported on pharmaceutical giant Eli Lilly’s own phase 3 clinical trial follow weekly tirzepatide injections compared to placebo injections among 1,032 participants over the course of roughly three years.

(Peter Dazeley/The Image Bank/Getty Images)

Not only did the medication cut health risks, those on the 15 mg per week dose lost an average of 22.9 percent of their body weight across the course of the research period, compared to a drop of just 2.1 percent for those taking a placebo treatment.

“Obesity is a chronic disease that puts nearly 900 million adults worldwide at an increased risk of other complications such as type 2 diabetes,” says Jeff Emmick, a senior vice president at Eli Lilly, which manufactures Zepbound.

“Tirzepatide reduced the risk of developing type 2 diabetes by 94 percent and resulted in sustained weight loss over the three-year treatment period.”

Keeping in mind the study’s details are yet to be peer-reviewed and published, the trial’s results strongly suggest that tirzepatide could significantly reduce the chance of type 2 diabetes developing in those who are already at high risk.

The likelihood of developing diabetes from a pre-diabetes stage for people over the age of 45 varies depending on individual circumstances, but it’s generally thought to be around 9 to 14 percent. We’re potentially talking about tens of millions of people who could delay or prevent the onset of a serious metabolic condition.

Like similar weight loss drugs developed in recent years, tirzepatide mimics the effects of natural hormones: specifically GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). These hormones improve blood sugar control and help to suppress appetite.

Tirzepatide has already been attracting a lot of attention: previous studies have put it at least on par of the similar Ozempic drug in the weight loss stakes. What’s more, there are indications that the health benefits of these treatments could go beyond weight loss.

These drugs aren’t without their drawbacks though. While approved for use by regulators, tirzepatide can lead to some pretty serious side effects in certain people, including stomach and kidney problems, low blood sugar, and serious allergic reactions.

Questions also remain about the long-term effectiveness of the treatment. In the 17 weeks following the trial, participants who had stopped taking tirzepatide began to regain weight, and some progression to type 2 diabetes was recorded. With these 17 weeks included, the risk reduction dropped to 88 percent.

While drugs such as these – including Zepbound and the related diabetes drug Mounjaro – shouldn’t be taken without professional advice, the research suggests that even more significant treatments are on the way to reduce type 2 diabetes risk.

“These data reinforces the potential clinical benefits of long-term therapy for people living with obesity and pre-diabetes,” says Emmick.

The research is due to be presented at Obesity Week 2024 at San Antonio in November.

Credit: www.sciencealert.com

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People who volunteer to donate a kidney face an even lower risk of death from the operation than doctors have long thought.

The study tracked 30 years of living kidney donation and found that by 2022, fewer than 1 of every 10,000 donors died within three months of the surgery. Transplant centers have been using older data – citing a risk of 3 deaths per 10,000 living donors – in counseling donors about potentially deadly surgical complications. “The last decade has become a lot more safe in the operating room for living donors,” said Dr. Dorry Segev, a transplant surgeon at NYU Langone Health. He co-authored the study published in the journal JAMA.

Newer surgical techniques are the key reason, said Segev, calling for guideline updates to reflect those safety improvements – and maybe increase interest in living donation.

He often finds transplant recipients more worried about potential risks to their donors than the would-be donors themselves.

“For them, this is even more reassuring to allow their friends or family to donate on their behalf,” Segev said.

Thousands of people die each year waiting for an organ transplant. It’s possible for living donors to give a one of their two kidneys or part of a liver, the only organ that regenerates.

With nearly 90,000 people on the U.S. list for a kidney transplant, finding a living donor not only shortens the yearslong wait — those organs also tend to survive longer than ones from deceased donors.

Yet last year, just 6,290 of the nation’s more than 27,000 kidney transplants came from living donors, the most since before the pandemic. Safety isn’t the only barrier to living donation. So is awareness, as many patients are reluctant to ask. And while the recipient’s insurance covers medical bills, some donors face expenses such as travel or lost wages as they recover.

The NYU team analyzed U.S. records of more than 164,000 living kidney donations from 1993 through 2022 and found 36 post-surgical deaths. Most at risk were male donors and those with a history of high blood pressure.

Only five of those deaths occurred since 2013. That period coincided with U.S. transplant centers switching to minimally invasive kidney removal as well as adopting a better way to stop renal artery bleeding, Segev said.

“Over time, it’s a safe operation that’s become even safer,” important for would-be donors to know, said Dr. Amit Tevar of the University of Pittsburgh Medical Center, who wasn’t involved in the study.

But there are long-term risks to consider, too, he stressed — including whether a donor’s remaining kidney is expected to last the rest of their life.

The risk of a donor later experiencing kidney failure also is small and depends on such factors as obesity, high blood pressure, smoking and family history of kidney disease. Risk calculators help doctors determine a potential donor’s likelihood of later-in-life trouble, and transplant centers may have slightly different eligibility criteria.

“There’s no such thing as a moderate- or high-risk donor — either you’re perfect or you’re not,” is how Tevar puts the decision to accept or turn away a potential donor.

Doctors once thought young adults were the ideal living donor. But Segev said there’s a shift toward more older living donors because it’s easier to correctly predict that they won’t outlive their remaining kidney.

If a living donor later experiences kidney failure, they get priority for a transplant, he noted.

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.

Credit: ABC News

Team Metabolic Health

A new study revealed children who go from normal weight to overweight have a greater risk of atopic dermatitis than obese children who maintain their weight.

A new study found children with obesity have an increased risk of pediatric immune-mediated skin diseases, particularly atopic dermatitis. Conversely, weight loss can lower the risk.

“This is the noteworthy longitudinal investigation that has revealed the association between BMI changes and subsequent occurrences of 3 main pediatric [immune-mediated skin diseases]—[alopecia areata, atopic dermatitis, and psoriasis]—as well as the direct influence of BMI on [alopecia areata],” wrote co-lead investigators Hyunsun Park, MD, PhD, Seong Rae Kim, MD, and Seong-Joon Koh, MD, PhD, from Seoul National University College of Medicine.

In recent years, immune-mediated skin diseases, such as alopecia areata, atopic dermatitis, and psoriasis have become a public health concern among children. These conditions harm the quality of life regarding emotional, physical, social, and functional well-being.

Obesity rates have also surged in the previous years. Research has suggested excessive adipose tissues may trigger proinflammatory mechanisms that lead to the development of skin diseases, however, this topic still needed further investigations as this was speculation. In this study, investigators wanted to understand better how childhood obesity or weight gain interacted with the development of pediatric immune-mediated skin diseases.

“Our research team is very interested in the skin-gut access,” said co-lead investigator Hyunsun Park, MD, PhD, from the department of dermatology at Seoul National University College of Medicine in Seoul, Republic of Korea. “We think that various factors, including diet, obesity, or other lifestyles can affect gut environment and contribute to the development of IMSDs. We are trying to find the puzzle pieces to demonstrate how they are connected, and our current research is a step towards that understanding.”

Thus, investigators, also co-led by Seong Rae Kim, MD, and Seong-Joon Koh, MD, PhD, both from the Seoul National University College of Medicine, conducted a study to assess the associations between body mass index (BMI) or BMI changes and the development of 3 immune-mediated skin diseases: alopecia areata, atopic dermatitis, and psoriasis.

The team analyzed a longitudinal cohort of 2,161,900 Korean children from 2009 to 2020. The sample included 10,524,561 person-years in the alopecia areata cohort, 6,910,806 person-years in the atopic dermatitis, and 10,530,018 person-years in the psoriasis cohort. Overall, the cases of immune-mediated skin diseases were 4,878 for alopecia areata (51.1% male), 41,386 for atopic dermatitis (50.4%); and 2,191 for psoriasis (51.1).

The findings demonstrated children with obesity had a greater risk of pediatric immune-mediated skin diseases than those with a normal weight (P < .01). Children who had an increase in BMI with a weight gain from normal to overweight had a greater risk of atopic dermatitis (adjusted hazard ratio [aHR], 1.15; 95% confidence interval [CI], 1.11 – 1.20). Reversely, a decrease in BMI—and weight loss from overweight to normal weight, had a lower atopic dermatitis risk than children who were overweight and maintained their weight (aHR, 0.87; 95% CI, 0.81 – 0.94; P < .001).

“Our findings support the importance of promoting weight maintenance among children who are already within the normal weight range because it may help reduce the risk of developing atopic dermatitis,” Koh said in the press release. “In addition, prevention of excessive weight gain and purposeful weight loss, including adopting healthy diet strategies in children with obesity to prevent atopic dermatitis, particularly before school age, should be promoted. Implementing purposeful interventions, including nutritional strategies, to decrease body weight may aid in reducing the risk of developing [immune-mediated skin diseases] in children.”

Credit: https://www.hcplive.com/

Team Metabolic Health

Researchers from the University of Cincinnati College of Medicine and Cincinnati Children’s Hospital have found a new method to increase both speed and success rates in drug discovery.

The study, published Aug. 30 in the journal Science Advances, offers renewed promise when it comes to discovering new drugs.

“The hope is we can speed up the timeline of drug discovery from years to months,” said Alex Thorman, PhD, co-first author and a postdoctoral fellow in the Department of Environmental and Public Health Sciences in the College of Medicine. 

Researchers combined two approaches for screening potential new drugs. First, they used a database from the Library of Integrated Network-based Cellular Signatures (LINCS) to screen tens of thousands of small molecules with potential therapeutic effects simultaneously. Then they combined the search with targeted docking simulations used to model the interaction between small molecules and their protein targets to find compounds of interest. That sped up the timing of the work from months to minutes -; taking weeks of work required for initial screening down to an afternoon.

Thorman said this faster screening method for compounds that could become drugs accelerates the drug research process. But it’s not only speed that is crucial. 

He added that this newer approach is more efficient at identifying potentially effective compounds. 

It can also create more targeted treatment options in precision medicine, an innovative approach to tailoring disease prevention and treatment that takes into account differences in people’s genes, environments and lifestyles. 

“An accelerated drug discovery process also could be a game changer in the ability to respond to public health crises, such as the COVID-19 pandemic,” said Thorman. “The timeline for developing effective drugs could be expedited.” 

The other co-first authors were Jim Reigle, PhD, a postdoctoral fellow at Cincinnati Children’s Hospital, and Somchai Chutipongtanate, PhD, an associate professor in the Department of Environmental and Public Health Sciences in the College of Medicine.

The corresponding authors of the study were Jarek Meller, PhD, a professor of biostatistics, health informatics and data sciences in the College of Medicine, and Andrew Herr, PhD, a professor of immunobiology in the Department of Pediatrics in the College of Medicine. 

Other co-investigators included Mario Medvedovic, PhD, professor and director of the Center for Biostatistics and Bioinformatics Services in the College of Medicine, and David Hildeman, PhD, professor of immunobiology in the College of Medicine. Both Herr and Hildeman have faculty research labs at Cincinnati Children’s Hospital. 

This research was funded in part by grants from the National Institutes of Health, a Department of Veterans Affairs merit award, a UC Cancer Center Pilot Project Award and a Cincinnati Children’s Hospital Innovation Fund award.

Those involved in the research are also co-inventors on three U.S. patents that are related to their work and have been filed by Cincinnati Children’s Hospital. 

Credit: University of Cincinnati

Team Metabolic Health

The numbers are staggering; right now, about 100,000 people are on a waitlist for a kidney transplant but there aren’t enough donors. While they haven’t perfected it, researchers are working to see if some animals might be able to fill the gap.

Pigs to the rescue: Revolutionizing kidney transplants© IVANHOE

When it comes to saving lives for people with kidney disease, the math just does not add up.

“When you think about 37 million Americans with chronic kidney disease and at any given time, [600,000] to 800,000 have actual kidney failure. And we only waitlist [80,000] to 100,000 and we only transplant 25,000,” said Jayme E. Locke, MD, MPH, Arnold G. Diethelm MD Endowed Chair in Transplantation Surgery at the University of Alabama at Birmingham, Heersink School of Medicine.

Researchers at the University of Alabama at Birmingham are some of the first to fill the need with xenotransplantation.

“The goal, of course, is to sort of really basically eliminate that gap between supply and demand. And in our case, we’re hoping to do that with pig organs. Well interestingly, pigs actually have kidney function that’s quite similar to human,” Locke said.

Researchers use a CRISPR, which is a genetic editing tool, to edit out genes that would cause a human body to reject the organ.

“It kind of tricks the human immune system into thinking it’s something from a human,” Locke adds.

And because pigs can live 30 years, researchers believe the organ will last that long for humans, and they hope to use more organs from pigs.

“And so, I think, certainly, those of us in xenotransplantation see a future in which one pig can donate a heart, a pair of lungs, a liver, a kidney, maybe even a pancreas,” Locke said.

Several pig organ transplant recipients have died in recent months following their operation. It’s important to remember that xenotransplantation is still very much in the experimental stages, but researchers are committed to perfecting this alternative source of organs when human organs are not available. The next step will be a clinical trial to seek FDA approval.

Credit: msn.com

Team Metabolic Health

A phase 2 trial met its primary endpoint, showing NBI-1117568, the first M4 selective agonist, is effective and safe at treating adult schizophrenia. Neurocrine Biosciences recently announced their phase 2 trial met its primary endpoint, demonstrating the effectiveness of NBI-1117568 for schizophrenia. The once-daily 20 mg dose of NBI-1117568 provided a statistically significant 7.5-point improvement in the Positive and Negative Syndrome Scale (PANSS) Total Score compared to the placebo at week 6 (P = .011; effect size of 0.61) with an 18.2-point PANSS Total Score Improvement from Baseline.

Eiry W. Roberts, MD Credit: LinkedIn

“This Phase 2 dose-finding study delivered on our goal of identifying a once-daily, well tolerated dosing regimen with a compelling and competitive benefit-risk profile,” said Eiry W. Roberts, MD, Chief Medical Officer at Neurocrine Biosciences, in a statement. “We recognize the significant need for new and innovative medicines to treat schizophrenia and look forward to advancing NBI-‘568, the first M4 selective agonist, into Phase 3 development early next year.”

According to the World Health Organization, approximately 20 million people worldwide experience schizophrenia. Traditional treatment options for schizophrenia often rely on antipsychotic medications which may lead to short- and long-term health impacts. Thus, investigators wanted to study a novel treatment option for schizophrenia.

Investigators conducted a phase 2, multicenter, randomized, double-blind, placebo-controlled, multi-arm, multi-stage inpatient dose-finding study to assess the efficacy, safety, tolerability, and pharmacokinetics of NBI-1117568 compared with placebo in adult patients with schizophrenia. The study included 210 participants with schizophrenia who experienced an acute exacerbation or relapse of symptoms.

Other than meeting the primary endpoint, the once-daily 20 mg dose of NBI-1117568 also provided significant improvement for secondary endpoints, including the Clinical Global Impression of Severity (CGI-S) scale, Marder Factor Score – Positive Symptom Change, and Marder Factor Score – Negative Symptom Change.

The trial showed NBI-1117568 was safe and well-tolerated at all doses. Investigators observed similar treatment discontinuation rates due to adverse events between participants on NBI-1117568 and placebo. The most common adverse events observed included somnolence, dizziness, and headache.

Less common adverse events included nausea and constipation, cardiovascular-related events, and extrapyramidal symptoms. Gastrointestinal adverse events were similar in both arms, and cardiovascular-related events did not seem to have clinical relevance at any dose. NBI-1117568 was not associated with greater weight gain when compared to placebo.

“NBI-1117568 demonstrated a clinically meaningful and statistically significant reduction in PANSS scores and was well tolerated, importantly with minimal GI effects and no weight gain relative to placebo,” said Maurizio Fava, Psychiatrist-in-Chief at Massachusetts General Hospital of Harvard University, in the press release. “As a selective M4 orthosteric agonist, the potential of NBI-1117568 as an option that could reduce symptoms of schizophrenia with fewer side effects would be a welcome alternative to current treatments for patients and caregivers.”

Credit: hcplive.com

Team Metabolic Health

Pfizer will work with the Flagship-funded Quotient Therapeutics to conduct research that will inform drug development for cardiovascular and renal diseases.

More than a year after Pfizer and venture capital company Flagship Pioneering struck a partnership investing in 10 life sciences programs, the two unveiled a collaboration with Quotient Therapeutics.

The Flagship-funded Quotient, which specializes in somatic genetics — or the study of mutations in somatic cells — will work with Pfizer to conduct research that can inform drug development for cardiovascular and renal diseases. Quotient was founded by Flagship in 2022. Financial terms of the deal were not disclosed.

Flagship’s drug discovery and development unit Pioneering Medicines will be responsible for spearheading the partnership with Pfizer, the company said in a press release. Quotient CEO Jacob Rubens the company’s Somatic Genomics platform as having the potential to investigate the “extensive genetic diversity” among 30 trillion cells in the body. He added that Pfizer’s involvement in these dual programs will allow for the research to scale.

Source: Getty Images

“This offers an incredibly rich and uncharted territory for drug discovery,” Rubens said in a statement. “These two research programs will deploy our unique platform capabilities to identify novel links between genes and cardiovascular or renal disease, which are leading causes of mortality and morbidity around the world.”

The collaboration is the latest update in the Pfizer and Flagship alliance, which was struck in July 2023 to develop a 10-program pipeline of innovative medicines to address unmet needs.

The pact, which involved both companies investing a total of $100 million upfront initially, allows Pfizer to choose from Flagship’s large ecosystem of 40 biotech companies to explore potential therapies.

In June, Pfizer and Flagship announced their first choice — a partnership with ProFound Therapeutics to investigate new weight loss drugs.

That collaboration entails ProFound using its proprietary ProFoundry Platform in combination with Pioneering Medicine’s drug development expertise to explore novel proteins as potential obesity therapies.

At the time, Charlotte Allerton, head of discovery and early development at Pfizer, noted that the partnership was designed to push the “boundaries of science to potentially unlock new protein therapeutics for obesity.”

The announcement also comes a day after Pfizer unveiled its direct-to-consumer (DTC) platform, PfizerForAll, following in the footsteps of Eli Lilly and Company in launching telehealth services. 

The goal is for consumers to access a one-stop-shop directly from the big pharma company to book in-person or telehealth appointments, receive home delivery for prescription drugs or schedule vaccinations.

Pfizer launched the platform a little less than a year after Lilly debuted its own DTC platform, LillyDirect.

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Team Metabolic Health

For a not insubstantial fee, many private clinics in the UK offer full-body MRI scans to detect disease and abnormalities at the earliest stage. Kim Kardashian and Kate Hudson are fans.

So how do these scans work and are they “life saving”, as Kardashian suggests?

MRI produces 3D detailed anatomical images of almost every internal structure in the human body, including the organs, bones, muscles and blood vessels. MRI scanners create images of the body using a large magnet and radio waves. Unlike X-rays or CT, it doesn’t rely on ionising radiation, which can very slightly increase the risk of cancer.

Prices of full body scans in the UK range from £1,000 to £3,000. While they give a good basic overview of your anatomy, they don’t optimise the view of each organ or system. Any unusual findings would need to be further investigated by specialised MRI scans for things such as the heart and prostate. This is because the machine needs to be adjusted to different parameters to optimise the imaging of different organs and systems.

It’s important to note that MRI scans cannot detect most preventable diseases. Heart disease, high blood pressure, high cholesterol and diabetes are responsible for most deaths. MRI scans cannot detect these conditions. They may show some structural changes, but other symptoms will probably have emerged first.

Full-body MRI scans may find abnormalities, often referred to as “incidentalomas” because they are just incidental findings, on scans being undertaken for other symptoms.

Studies looking at over 16,000 brain MRI scans of volunteers have shown that less than 4% of them contained abnormalities that required further investigation.

The kind of things found on brain scans include pituitary abnormalities, such as non-cancerous growths. Disrupted blood flow to the brain (without symptoms) has been detected in 7%, aneurysms in 1.8% and benign tumours in 1.6% of the population.

Small clusters of abnormal blood vessels, known as cavernomas, rarely cause symptoms and are seen in about one in 600 people on MRI scans. Those that do cause symptoms are seen in about one in 400,000 people.

Another area of the body that often throws up incidental findings is the spine. There is increasing use of MRI in back pain. This can lead to the discovery of incidentalomas such as harmless bone growths and haemangiomas, small growths of blood vessels on or in the spine.

Haemangiomas are seen in over 40% of people who receive MRI scans, 99% of which cause no symptoms and don’t need treatment. The 1% who have symptoms, such as pain, numbness or weakness, require surgery to prevent progression towards paralysis.

Tarlov cysts, an outpouching around nerves leaving the spinal cord in the sacral region (near the bottom of the spine) are seen in about 4% of the population. For most, there are no symptoms. But those who have symptoms, such as pain and numbness, may need surgery to prevent bone decay or damage to the nerve supply to the legs, pelvic structures and genitals.

Kim Kardashian wrote about her full-body scan on Instagram. Imago/Alamy Stock Photo

What about serious findings?

A meta-analysis (a study that combines data from many studies) suggests that serious problems that are picked up by chance on MRI scans are 1.4% for the brain, 1.3% for the chest and 1.9% for the abdomen.

There is also a risk that these scans give a false positive – things that look like disease but aren’t. Breasts (up to 97 false positives per 1,000 scans) and prostate (29 per 100 scans) are particularly susceptible to false positive results.

These scans may give some valuable information about what is going on beneath your skin. However, for many people, the reports and terminology used in them are hard to fathom. There is lots of evidence that the average person struggles to understand common medical phrases and often assign meaning opposite to what the doctor intended – for a single diagnosis. Reports resulting from these scans are about the whole body and will contain significantly higher levels of medical information than a single diagnosis – even when everything is normal.

Where people pay for these scans without the wherewithal to cover any follow-up medical investigation, it will be already overstretched healthcare systems that have to pick up the fallout and ensure that false positives and benign growths are confirmed as such.

These scans offer an opportunity to see what’s going on internally – for those with enough money to afford them – but the likelihood of finding something that needs urgent medical treatment is low. If I had the money to spend on one of these, I’d spend it on a holiday, which would be far better for my health.

Credit: The Conversation

Team Metabolic Health

In June, Gilead Sciences announced impressive early results from its PURPOSE 1 trial, which showed 100 percent efficacy of lenacapavir in preventing new HIV infections among cisgender women in Sub-Saharan Africa. Lenacapavir is being investigated as an injectable antiretroviral medication that can be taken once every six months as preexposure prophylaxis (PrEP) to prevent HIV. This is a marked shift from current PrEP options, which are only available as a once-daily pill or a bimonthly injection.

Once again, the HIV community finds itself at a scientific breakthrough moment. And once again, it remains an open question as to whether it will also prove to be a breakthrough moment for equitable access.

We have been down this road before. It was not so long ago that the very same drug manufacturer released similarly jaw dropping clinical trial results first for Truvada and then Descovy, the first two medications approved for the prevention of HIV; it led to widespread speculation of the end of HIV as an epidemic. And yet, more than a decade after the first approval for PrEP in the United States, we still see significant disparities in getting PrEP to communities of color and cisgender women in the US.

Health care advocates are already concerned that past will once again be prologue when it comes to this new PrEP modality, and there is pressure on the company to make commitments that could change all too predictable outcomes on disparate outcomes.

The $40,000 Question

The big question of course will be the price set for lenacapavir’s PrEP indication in the US. We already have some insight here. In May 2019, Gilead received Food and Drug Administration (FDA) approval for a limited HIV treatment indication for lenacapavir for individuals for whom other HIV treatment regimens have not worked. The drug is sold under the brand name Sunlenca, which Gilead launched with a list price of $42,250 per year. To put the Sunlenca price tag in context, the list price of Gilead’s leading brand-name oral medication for PrEP, Descovy, comes in at about $26,000 per year. The bimonthly injectable PrEP option made by Gilead’s competitor, ViiV Healthcare, comes in at a comparable $23,000 per year.

There is no reason to think that as the indication of lenacapavir expands to PrEP, Gilead will back down from its initial high price. And again, we don’t need to guess here, we need only look at past actions. The pricing strategy that Gilead used to set the whopping $1,000-per-pill list price for its curative treatment for hepatitis C was fully explicated in a congressional oversight report, which found that Gilead’s goal was “maximizing revenue, regardless of the human consequences.”

To be clear, the list price is and has always been a bit of a fiction. With the availability of rebates and discounts and low-income assistance programs, few payers or even consumers will ever pay close to that amount. But it does matter. The list price sets the ceiling from which the complex set of drug distribution players in the US negotiate a lower price. Start high and even with discounts, we’ll end high. For a drug with such public health significance as PrEP, the high list price also hamstrings the ability of state and local public health departments that perennially struggle with anemic budgets—some of whom qualify for discounts and some of whom do not—to purchase the drug and get it out to uninsured, low-income, and vulnerable populations.

Other innovative purchasing strategies, such as a subscription model in which safety-net programs pay manufacturers a set negotiated amount for unlimited access to a drug, may be another consideration for PrEP. Subscription models have gotten some traction as a way for state Medicaid programs to cover costly hepatitis C curative treatments, but much more work has to be done to assess how a subscription model might be applied to PrEP, where the volume is lower and where there are multiple effective regimens, including low-cost generics, on the market.

Finally, the high list price locks us into fragmented delivery from the very beginning. Low-income individuals without insurance will be dependent on manufacturer patient assistance to help them access lenacapavir. Those programs will only provide access to the drug and not any other services people need to actually take the drug, including the recommended HIV, sexually transmitted disease, and other testing recommended to safely take PrEP. So instead of a public health program that is able to provide integrated access to PrEP services—including the medication—consumers will have to navigate a web of disparate programs to patch together all the services they need.

As we’ve seen with numerous other new-to-market drugs, a high list price for lenacapavir for PrEP will profoundly limit access for millions of uninsured Americans—a group that is disproportionately Black, Brown, and transgender and gender nonconforming. As noted above, the price point forecloses a public health response to PrEP, forcing individuals to jump through complex hoops to cobble together access. The decision on price made now could set the stage for more than a decade of inequitable access; Gilead has indicated in its most recent 10-K filing (page 7) that it expects lenacapavir to remain on patent and face no significant competition until 2037.

But Wait, Does Research And Development Justify A High Price?

Developing a new drug is an expensive endeavor. And indeed, high price tags are often justified by pointing to the immense costs of research and development. To be fair, Gilead undoubtedly invested in its PURPOSE trials, which have been far more comprehensive than the trials the company oversaw to secure a PrEP indication for Descovy, for which Gilead primarily conducted research among White gay and bisexual men and completely excluded cisgender women and transgender men.

But the cries that high prices are necessary for innovation seem somewhat disingenuous when they are rarely backed by transparency around the funding mix that goes into research and development of any one drug. And such claims deserve scrutiny when researchers have recently shown that lenacapavir could be made for less than $40 per person each year.

Past, again, may be prologue here. According to a Senate Finance Committee report on the development and marketing of Sovaldi, the first curative therapy for hepatitis C, “Gilead failed to provide costs attributable solely to the development of” its blockbuster hepatitis C cure despite repeated requests from Congress. The company from which Gilead acquired sofosbuvir estimated that the final Phase 3 studies would cost only $125.6 million, nowhere near an amount that would justify a $1,000-per-pill price tag. Following the December 2013 FDA approval, Gilead recouped its research costs and then some with $10.3 billion in 2014 sales of stand-alone sofosbuvir along with $2.1 billion in 2014 sales for Harvoni, a single tablet regimen of sofosbuvir combined with another direct-acting antiviral.

Recent research has also unearthed a very different investment story supporting the research and development for Gilead’s first approved PrEP medication, Truvada, finding that the federal government invested $143 million in the research leading to Truvada’s approval, far more than initially estimated and undermining Gilead’s justifications for steep price increases for Truvada following its July 2012 FDA approval as PrEP.

To be fair, developing breakthrough medications requires investment, and manufacturers should have incentives to embark on the long and arduous process of drug development that more often than not leads to a lot of failures before success. However, we should interrogate assertions that any policy aimed at identifying a fair price will imperil research and development incentives. Researchers have directly contradicted this assertion, modeling the impact of federal drug pricing reform and finding that the impact on new drugs coming to market is minimal.

What Can We Do Differently?

There is always hope we will learn from our past mistakes and do things differently the next time around. Advocates and academics alike have been calling for a federally funded national PrEP program to ensure widespread access to PrEP, particularly for un- and underinsured individuals. President Joe Biden included the program in his last three budget requests to Congress; it would provide the infrastructure necessary for the government to work meaningfully with Gilead to come up with an access strategy for lenacapavir at a price point that would work for a public health response. Should that come to pass, the US could really see the potential of this innovation for communities other than cisgender White men.

But even in a scenario in which the government steps in to work with Gilead to solve the access problem for uninsured populations, this pricing will create the same challenges for insured populations that have always existed in the US. Insurers will be absolutely disincentivized to encourage new PrEP users to access lenacapavir, particularly with affordable daily oral generic options at less than $20 per month. And with a price point for lenacapavir $10,000 to $15,000 above Descovy per year, we can anticipate payers’ strong resistance to even transitioning existing PrEP users over to lenacapavir. Even with a US Preventive Services Task Force Grade A for PrEP, which because of an Affordable Care Act (ACA) provision requires most private insurance plans to cover PrEP without cost sharing, there is no mandate for private insurance plans to cover every formulation of PrEP. Efforts are underway to improve insurance compliance with the ACA preventive services requirements for PrEP in general, but that advocacy faces an uphill road when Gilead is able to set whatever arbitrary starting price point it wants.

Another concern is that as new products, such as lenacapavir, come online, fullcourt marketing efforts may undercut the nascent market for generic oral forms of PrEP, which are safe, effective, and at less than $1 per pill, high quality but dirt cheap. This is exactly what happened when Gilead’s new oral PrEP regimen was approved the year before its first brand-name project went generic.

In the US, newer is often automatically dubbed better. And while the clinical trial results for lenacapavir are certainly impressive, it is not at all clear that the future of PrEP should be to push everyone onto long-acting brand-name products. Given the dismal uptake during these first few years of Apretude, the ViiV long-acting injectable for PrEP, it is also unclear if the market for long-acting products is quite as large as manufacturers say it is. At the end of the day, choice of the PrEP product that works best for the individual is the gold standard. What makes that choice possible is a fair price.

In the face of seemingly intractable drug access challenges in this country, there is still always the potential for an alternative future here. We can envision a scenario in which Gilead—perhaps facing significant pressure from the US advocacy community and the US government—commits to working with existing public health programs and, eventually, a national PrEP program to set a public health price point for lenacapavir to ensure a simple, transparent, and intuitive pathway for uninsured populations. This would be a new, bold approach—not a repeat of past charitable and donation programs that fail to provide an integrated approach to PrEP delivery. Instead, it would be a true, significantly lower price point that empowers public programs and health departments to come up with simple and comprehensive financing and delivery mechanisms that are highly accessible for end users. Only then will we stop repeating the same pattern in which the bang of a big scientific breakthrough is followed by the whimper of inaccessibility.

Credit: healthaffairs.org        

Team Metabolic Health

Common Lifestyle Mistakes

You may be unknowingly making some common mistakes that may impact your nervous system. It can affect nervous system regulation and also contribute to chronic stress, as opposed to reducing it. It is important to make a few small changes to your routine that can make a big difference. Scroll down to find out about the five simple habits that you need to change.

Checking Your Phone

Avoid checking your phone the moment you wake up. It can trigger a stress response by overwhelming you with notifications in the form of work emails and social media updates, says Marina Wright, a nutritionist.

Not Taking Breaks

You must take breaks from work, because constantly working without a pause can lead to ‘mental fatigue’ and reduced productivity, the nutritionist says, adding that it can keep the nervous system in a state of ‘continuous activation’.

Skipping Meals

According to Wright, skipping meals can cause your blood sugar levels to drop. It can trigger a stress response and disrupt the normal functioning of the nervous system. Skipping a meal can also lead to irritability, anxiety and fatigue. 

Spending Time Indoors

It is not wise to spend time indoors all day every day. It can limit your exposure to natural light, which can impact your mood negatively, and also increase stress. When there is a lack of sunlight, your circadian rhythm gets affected and you may feel a drop in energy levels.

Too Much Caffeine

Overconsumption of caffeine can stimulate the nervous system, and not in a good way. According to the expert, too much caffeine can put you in a constant state of alertness that can heighten your stress and anxiety. Consuming it late in the day can also disrupt your sleep. 

Credit: thehealthsite.com